Summary of Work: Metabolism by sulfotransferases is an inactivation of biological signals such as steroid hormones and also a defense system against environmental toxicants and carcinogens. To encounter virtually unlimited numbers of structurally diverse chemiclas, these enzymes exhibit broad substrate specificity. Thus, it is important to investigate the structural principle determining the substrate specificity in order to predict the metabolisms and the resulted consequences to human susceptibililty to chemical exposure. For the investigation, we have used x-ray crystallography and site-directed mutagenesis. We have solved the crystal structure of estrogen, hydroxyteroid, and phenol sulfotransferases.These structures provided the insight into understanding the reaction mechanism catalyzed by sulfotransferase. Site-directed mutagenesis based on the crytal structres defined a stricture-like gate that determines substrate specificity and also the common dimer interface for all cytosolic sulfotransferase. Sulfotransferases and glycosyltransferases are involved in glycosaminylglycan synthesis of proteoglycans. We have solved the crystal structures of heparan sulfate N-deacetylase/N-sulfotrabsferase and glucuronosyltransferase 1 and of glucuronytransferase 1.